Environmental toxins exert damaging health effects in workers. Thousands of responders who worked or volunteered on the World Trade Center (WTC) rescue and recovery effort following the September 11, 2001 attacks suffer from health conditions or may be at increased risk for worsening health. In a pilot study, we have identified the first evidence of kidney damage in subjects with very high exposure at Ground Zero. Specifically, we note a preliminary association between the intensity of particulate mater exposure and albuminuria, a marker of early chronic kidney disease (CKD), systemic endothelial dysfunction, and increased cardiovascular risk. Our long-term goal is to minimize the risk of CKD and cardiovascular disease (CVD) among individuals exposed to inhaled toxins. The primary objective of the current proposal is to quantify the risk of kidney damage among first responders to the WTC attack and to determine the relationship to particulate matter exposure. We will also leverage existing resources in our WTC Center of Excellence to study the association between renal and cardiovascular damage in first responders and to explore potential mechanisms. Our central hypothesis is that exposure to inhaled particulate matter causes systemic inflammation and endothelial dysfunction that result in chronic kidney and cardiovascular damage. We will investigate this hypothesis in a subgroup of participants in the on-going NIOSH-funded study Pulmonary Function Abnormalities, Diastolic Dysfunction and WTC Exposure: Implications for Diagnosis and Treatment (WTC-CHEST, PI Mary Ann McLaughlin). The proposed study will capitalize on unique resources in WTC-CHEST, including the standardized collection of data on particulate matter exposure and shared risk factors for CKD and cardiovascular disease, and cardiopulmonary function testing. The output from this proposal is anticipated to have a broad impact on understanding the health effects of inhaled particulate matter.